title: Tumor-specific urinary matrix metalloproteinase fingerprinting: identification of high molecular weight urinary matrix metalloproteinase species.
abstract: OBJECTIVE
  We have previously reported that matrix metalloproteinases MMP-2, MMP-9, and the complex MMP-9/NGAL can be detected in urine of patients with a variety of cancers including prostate and bladder carcinoma. In addition, we also detected several unidentified urinary gelatinase activities with molecular weights >125 kDa. The objective of the current study was to identify these high molecular weight (HMW) species, determine their potential as predictors of disease status, and ask whether a tumor-specific pattern existed based on urinary MMP analysis.
  
  
  METHODS
  Chromatography, zymography, and mass spectrometry was used to identify HMW gelatinase species of approximately 140, 190, and >220 kDa in urine of cancer patients. To determine whether a tumor-specific pattern of appearance existed among the MMPs detected, we analyzed the urine of 189 patients with prostate or bladder cancer and controls.
  
  
  RESULTS
  The approximately 140, >220 kDa, and approximately 190 HMW gelatinase species were identified as MMP-9/tissue inhibitor of metalloproteinase 1 complex, MMP-9 dimer, and ADAMTS-7, respectively. The frequency of detection of any MMP species was significantly higher in urine from prostate and bladder cancer groups than controls. MMP-9 dimer and MMP-9 were independent predictors for distinguishing between patients with prostate and bladder cancer (P < 0.001 for each) by multivariable analysis.
  
  
  CONCLUSIONS
  This study is the first to identify a tumor-specific urinary MMP fingerprint that may noninvasively facilitate identification of cancer presence and type. This information may be of diagnostic and prognostic value in the detection and/or clinical monitoring of disease progression and therapeutic efficacy in patients with bladder or prostate cancer.
authors.affiliation: Department of Surgery, Children's Hospital, Boston, MA 02115, USA.
authors.forename: Roopali
authors.initials: R
authors.lastname: Roy
authors.forename: Gwendolyn
authors.initials: G
authors.lastname: Louis
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Loughlin
authors.forename: Dmitri
authors.initials: D
authors.lastname: Wiederschain
authors.forename: Susan M
authors.initials: SM
authors.lastname: Kilroy
authors.forename: Carolyn C
authors.initials: CC
authors.lastname: Lamb
authors.forename: David
authors.initials: D
authors.lastname: Zurakowski
authors.forename: Marsha A
authors.initials: MA
authors.lastname: Moses
mesh_terms: D051722:ADAM Proteins / Q000652:urine; D000071118:ADAMTS7 Protein; D014408:Biomarkers, Tumor / Q000652:urine*; D016022:Case-Control Studies; D019281:Dimerization; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000652:urine*; D020780:Matrix Metalloproteinase 9 / Q000652:urine*; D008970:Molecular Weight; D009367:Neoplasm Staging; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000652:urine; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000652:urine; D001749:Urinary Bladder Neoplasms / Q000201:enzymology* / Q000652:urine
chemical_list: D014408:Biomarkers, Tumor; D019715:Tissue Inhibitor of Metalloproteinase-1; D051722:ADAM Proteins; D000071118:ADAMTS7 Protein; C121534:ADAMTS7 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9